Project Summary Antimicrobial innovation has slowed to a crawl while an epidemic of antimicrobial-resistant infections surges, threatening the public health. The overarching goal of the Wisconsin Antimicrobial Drug Discovery and Development Center is to develop therapeutic countermeasures to tackle the antimicrobial resistance crisis. Based upon our preliminary data, we hypothesize that natural product exploration of symbiotic environments using complementary cutting-edge approaches will provide a new paradigm for discovery of novel antimicrobials targeting drug resistant infections. The Center proposes innovative conceptual and technical advances to overcome critical bottlenecks identified in traditional antimicrobial drug discovery platforms. The success of this endeavor hinges upon the cohesive efforts from a diverse group of scientists and technical resources. The Administrative Core will be directed by Andes and advised by an Internal and External Advisory Board comprised of experts in infectious diseases, antimicrobial resistance, drug discovery and development, natural products, and technology transfer and licensing. Additionally, it will include an administrator with extensive experience in research and business administration, and prior oversight of NIH funded program projects and centers. The overall goals of the administrative core are to provide leadership and the organizational back bone for this proposal, promote collaboration between the Projects and Cores, and coordinate its interaction with NIAID staff. Relevance There are no effective therapies for the emerging resistant pathogens that are becoming an increasing threat to the public health. The goals of the Center are to provide new, broad spectrum antimicrobial agents through a collaborative focus on high value natural product leads produced by under-explored sources of biological divers ity.